Study of new therapeutic approaches on the treatment of chronic rhinosinusitis with nasal polyps

• Grant number: 19/05843-2
• Support type: Research Projects - Thematic Grants
• Duration: February 01, 2020 - January 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Fabiana Cardoso Pereira Valera
• Grantee: Fabiana Cardoso Pereira Valera
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Assoc. researchers: Armando da Silva Cunha Junior ; Edwin Tamashiro ; Eurico de Arruda Neto ; Marcello Rubens Barsi Andreeta ; Marina Trevelin Souza ; Oscar Peitl Filho ; Wilma Terezinha Anselmo-Lima

Abstract

Chronic Rhinosinusitis (CRS) is an inflammatory disease with high prevalence and considerable negative impact on quality of life and socioeconomic aspects. CRS is subdivided into two entities, being the chronic rhinosinusitis with nasal polyps (CRSwNP) a distinct disease due to its unique phenotype and physiopathogenesis, besides its unfavorable outcome. Around 40% of CRSwNP patients persist with symptoms and signs related to the disease, even following optimized treatment. Considering this clinical scenario, the current project aims, through four linked subprojects, to explore different signalling pathways, and to propose new therapies and new techniques for administering current drugs to treat CRSwNP, with the final purpose to improve the success rates of clinical treatment of CRSwNP. The subproject 1 will assess the caspase inhibitor pathway influence on the physiopathogenesis of CRSwNP and on the efficacy of topical corticosteroid treatment. Subproject 2 will explore in animal model (mice) the safety and efficacy of two distinct drug classes that were shown by in vitro studies to inhibit the inflammatory process in nasal polyps (ROCK inhibitors and potassium agonists). Subproject 3 will assess the effect of bioglass F18 in inhibiting Staphylococcus aureus (SA) biofilm formation in vitro, and the safety of this compound in an animal model (rabbit), in addition to its efficacy in controlling sinonasal inflammation. Subproject 4 will evaluate the safety and the efficacy of a new way of administering topical mometasone, by using a mucoadhesive with PLGA (polymer with lactic co-glycolic acid, which promotes slow and gradual programmed drug exposure), in an animal model (rabbits) and in a clinical phases I/II study. All subprojects have the potential to show clinical applicability at short to medium term. (AU)